Long-term follow-up of children with postnatal immunoprophylaxis failure who were infected with hepatitis B virus surface antigen gene mutant

Abstract

Background. The long-term evolution and outcomes of infection with a hepatitis B virus (HBV) surface antigen (HBsAg) gene mutant (hereafter, "HBsAg-mutant HBV") among immunized children remain unclear.Methods. Ninety-five HBsAg-positive children aged 0.5-18.4 years (mean age, 5.8 years) who did not respond to postnatal immunoprophylaxis were prospectively followed for 1-22.8 years (mean follow-up, 8.5 years). Clinical, serologic, and virologic features were compared between 38 untreated HBV e antigen (HBeAg)-positive children carrying HBsAg-mutant HBV (group 1) and 49 children carrying wild-type HBV (group 2). HBsAg-mutant HBV was examined in 20 immunized children presenting with HBV-related hepatocellular carcinoma (HCC).Results. The initial alanine aminotransferase (ALT) level, the maximal ALT level during the HBeAg-positive phase of HBV infection, the cumulative incidence of HBeAg seroconversion (P =. 0018), and the rate of low serum HBV DNA load (defined as <104 copies/mL) at the last visit (P =. 006) were higher in group 1 than in group 2. A higher frequency of HBV genotype C and a higher ALT level during surface mutant viremia were observed in codon 110-129 mutants than in codon 144-145 mutants. None of the 95 patients developed cirrhosis or HCC. HBsAg-mutant HBV was detected in 3 of 8 (38%) HBV DNA-positive children with HCC.Conclusions. HBeAg-positive immunized children carrying HBsAg-mutant HBV may develop hepatitis activity, HBeAg seroconversion, and a low viremic state earlier than those carrying wild-type HBV. Continuous monitoring of children with wild-type HBV infection and those with HBsAg-mutant HBV for possible development of HCC is needed. © 2013 The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.